NM_000489.6(ATRX):c.109C>T (p.Arg37Ter) AND Mental retardation-hypotonic facies syndrome, X-linked

Clinical significance:Pathogenic (Last evaluated: Dec 1, 2004)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000012508.23

Allele description [Variation Report for NM_000489.6(ATRX):c.109C>T (p.Arg37Ter)]

NM_000489.6(ATRX):c.109C>T (p.Arg37Ter)

Gene:
ATRX:ATRX chromatin remodeler [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq21.1
Genomic location:
Preferred name:
NM_000489.6(ATRX):c.109C>T (p.Arg37Ter)
HGVS:
  • NC_000023.11:g.77717155G>A
  • NG_008838.3:g.74115C>T
  • NM_000489.6:c.109C>TMANE SELECT
  • NM_138270.5:c.109C>T
  • NP_000480.3:p.Arg37Ter
  • NP_612114.2:p.Arg37Ter
  • LRG_1153:g.74115C>T
  • NC_000023.10:g.76972632G>A
  • NM_000489.3:c.109C>T
  • NM_000489.4:c.109C>T
  • g.76972632G>A
Protein change:
R37*; ARG37TER
Links:
OMIM: 300032.0022; dbSNP: rs122445108
NCBI 1000 Genomes Browser:
rs122445108
Molecular consequence:
  • NM_000489.6:c.109C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_138270.5:c.109C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Mental retardation-hypotonic facies syndrome, X-linked
Identifiers:
MedGen: C4016452

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000032742OMIMno assertion criteria providedPathogenic
(Dec 1, 2004)
germlineliterature only

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A nonsense mutation of the ATRX gene causing mild mental retardation and epilepsy.

Guerrini R, Shanahan JL, Carrozzo R, Bonanni P, Higgs DR, Gibbons RJ.

Ann Neurol. 2000 Jan;47(1):117-21.

PubMed [citation]
PMID:
10632111

Attenuation of an amino-terminal premature stop codon mutation in the ATRX gene by an alternative mode of translational initiation.

Howard MT, Malik N, Anderson CB, Voskuil JL, Atkins JF, Gibbons RJ.

J Med Genet. 2004 Dec;41(12):951-6. No abstract available.

PubMed [citation]
PMID:
15591283
PMCID:
PMC1735636
See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000032742.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (4)

Description

In 4 male cousins with the X-linked mental retardation-hypotonic facies syndrome (309580), Guerrini et al. (2000) identified a 109C-T transition in exon 2 of the ATRX gene, resulting in an arg37-to-ter (R37X) substitution. Two patients had moderate to profound mental retardation and the typical facial features of the syndrome, whereas the other 2 patients presented with mild mental retardation and epilepsy, but without the characteristic facial dysmorphism.

Howard et al. (2004) found that human embryonic kidney cells carrying the R37X mutation expressed approximately 20% of a slightly shortened ATRX protein compared to controls. Analysis of the 5-prime end of the ATRX gene revealed a downstream AUG start codon at residue 40, suggesting an alternative initiation event. Howard et al. (2004) suggested that 'phenotypic rescue' due to the expression of a truncated ATRX protein using the alternative downstream initiation site underlies the relatively mild phenotype seen in some patients with the R37X mutation.

Abidi et al. (2005) identified the R37X mutation in 3 affected males originally reported by Chudley et al. (1988) as having Chudley-Lowry syndrome. Western blot and immunocytochemical analyses using a specific monoclonal antibody directed against ATRX showed the protein to be present in lymphoblastoid cells, despite the premature stop codon. Abidi et al. (2005) suggested that the less severe phenotype was due to the presence of some residual ATRX protein. The phenotypic variation between patients with the same mutation suggested that the ATRX gene may influence the expression of several genes in multiple tissues during development.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 4, 2021

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